The objectives of this research proposal are: 1) to characterize immunologically and ultrastructurally the large body of neglected malignant lymphomas of extra-nodal origin; 2) to relate the results to the clinicopathologic features of these neoplasms and in so doing to; and 3) eventually be able to clearly distinguish benign from malignant lymphoreticular proliferations that commonly occur in the ocular tissues, skin, gastrointestinal tract, salivary glands and other extra-nodal sites. The methodology consists of the application to the extra-nodal lymphoid neoplasms of the in vitro immunologic, histochemical, immuno-histochemical and electron microscopic techniques already of proved value in the study of the systemic nodal malignant lymphomas. The systematic serial study of freshly obtained biopsy specimens processed for in vitro immunologic studies and for immunoperoxidase and histochemical studies of formalin fixed and cryostat sections will permit correlation of the topographic orientation and interrelationships in tissue sections of the lymphoid populations more fully characterized by the in vitro immunologic studies. The central premise to be tested is that benign lymphoid hyperplasias are composed of polyclonal cell populations while malignant lymphoid neoplasms are monoclonal. Information derived from these studies may become a cornerstone in the diagnosis of patients with extra-nodal lymphomas as well be a determining factor in therapy and prognosis.